Abstract
Background: The transcription factor Nrf2 regulates expression of multiple cellular defence proteins through the antioxidant response element (ARE). Nrf2-deficient mice (Nrf2-/-) are highly susceptible to xenobiotic-mediated toxicity, but it is not known whether this reflects low basal expression or reduced inducibility of Nrf2-regulated genes in response to chemical insults. Methods: Wild type and Nrf2-/- mice were fed diet supplemented with the established Nrf2 inducer butylated hydroxyanisole (BHA) [0.5% (w/w)] for 14 days. To define the range of Nrf2-regulated proteins, both basally and following exposure to BHA, a comparison of the liver proteomes of Nrf2-/- and wild type mice was conducted. The two-dimensional gel electrophoresis (2-DE) technique and MALDI mass spectrometry were utilized in the attempt to define Nrf2-regulated proteins. Results: Overall, 24 proteins were identified, which were regulated either basally (3 proteins), inducibly (16 proteins), or both (5 proteins). These included several well-established Nrf2-driven gene products e.g., aldo-keto reductase and glutathione transferases. Multiple consensus ARE/ARE-like sequences were found in the Nrf2-regulated genes. Conclusions: This study confirms the central role of Nrf2 in the induction of multiple defense proteins as well as its control in the constitutive expression of certain proteins.
| Original language | English |
|---|---|
| Pages (from-to) | 680-697 |
| Number of pages | 18 |
| Journal | Pharmacological Reports |
| Volume | 64 |
| Issue number | 3 |
| Publication status | Published - 2012 |
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Keywords
- Liver
- Mouse
- Nrf2
- Protein expression
- Transgenic
- Two-dimensional gel electrophoresis
ASJC Scopus subject areas
- Pharmacology
Cite this
Analysis of the role of Nrf2 in the expression of liver proteins in mice using two-dimensional gel-based proteomics. / Abdullah, Azman; Kitteringham, Neil R.; Jenkins, Rosalind E.; Goldring, Christopher; Higgins, Larry; Yamamoto, Masayuki; Hayes, John; Park, B. Kevin.
In: Pharmacological Reports, Vol. 64, No. 3, 2012, p. 680-697.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Analysis of the role of Nrf2 in the expression of liver proteins in mice using two-dimensional gel-based proteomics
AU - Abdullah, Azman
AU - Kitteringham, Neil R.
AU - Jenkins, Rosalind E.
AU - Goldring, Christopher
AU - Higgins, Larry
AU - Yamamoto, Masayuki
AU - Hayes, John
AU - Park, B. Kevin
PY - 2012
Y1 - 2012
N2 - Background: The transcription factor Nrf2 regulates expression of multiple cellular defence proteins through the antioxidant response element (ARE). Nrf2-deficient mice (Nrf2-/-) are highly susceptible to xenobiotic-mediated toxicity, but it is not known whether this reflects low basal expression or reduced inducibility of Nrf2-regulated genes in response to chemical insults. Methods: Wild type and Nrf2-/- mice were fed diet supplemented with the established Nrf2 inducer butylated hydroxyanisole (BHA) [0.5% (w/w)] for 14 days. To define the range of Nrf2-regulated proteins, both basally and following exposure to BHA, a comparison of the liver proteomes of Nrf2-/- and wild type mice was conducted. The two-dimensional gel electrophoresis (2-DE) technique and MALDI mass spectrometry were utilized in the attempt to define Nrf2-regulated proteins. Results: Overall, 24 proteins were identified, which were regulated either basally (3 proteins), inducibly (16 proteins), or both (5 proteins). These included several well-established Nrf2-driven gene products e.g., aldo-keto reductase and glutathione transferases. Multiple consensus ARE/ARE-like sequences were found in the Nrf2-regulated genes. Conclusions: This study confirms the central role of Nrf2 in the induction of multiple defense proteins as well as its control in the constitutive expression of certain proteins.
AB - Background: The transcription factor Nrf2 regulates expression of multiple cellular defence proteins through the antioxidant response element (ARE). Nrf2-deficient mice (Nrf2-/-) are highly susceptible to xenobiotic-mediated toxicity, but it is not known whether this reflects low basal expression or reduced inducibility of Nrf2-regulated genes in response to chemical insults. Methods: Wild type and Nrf2-/- mice were fed diet supplemented with the established Nrf2 inducer butylated hydroxyanisole (BHA) [0.5% (w/w)] for 14 days. To define the range of Nrf2-regulated proteins, both basally and following exposure to BHA, a comparison of the liver proteomes of Nrf2-/- and wild type mice was conducted. The two-dimensional gel electrophoresis (2-DE) technique and MALDI mass spectrometry were utilized in the attempt to define Nrf2-regulated proteins. Results: Overall, 24 proteins were identified, which were regulated either basally (3 proteins), inducibly (16 proteins), or both (5 proteins). These included several well-established Nrf2-driven gene products e.g., aldo-keto reductase and glutathione transferases. Multiple consensus ARE/ARE-like sequences were found in the Nrf2-regulated genes. Conclusions: This study confirms the central role of Nrf2 in the induction of multiple defense proteins as well as its control in the constitutive expression of certain proteins.
KW - Liver
KW - Mouse
KW - Nrf2
KW - Protein expression
KW - Transgenic
KW - Two-dimensional gel electrophoresis
UR - http://www.scopus.com/inward/record.url?scp=84866136122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866136122&partnerID=8YFLogxK
M3 - Article
C2 - 22814021
AN - SCOPUS:84866136122
VL - 64
SP - 680
EP - 697
JO - Pharmacological Reports
JF - Pharmacological Reports
SN - 1734-1140
IS - 3
ER -